The Regulatory Knowledge Core (RKC) is a vital component of the Collaborative Research Center for American Indian Health (CRCAIH). The mission of the RKC is to offer regulatory support and create a research infrastructure for investigators and participating institutions to ensure responsible conduct of research, community ownership of the research review process and the highest level of human subjects protection. The framework set forth by the RKC will facilitate investigators and member institutions in navigating the regulations governing human subjects research and will serve as an integrated pathway for all regulatory needs of the CRCAIH. The RKC will work in close collaboration with the Culture, Science and Bioethics Core and Methodology Core to create an ideal environment for the execution of high quality transdisciplinary community-based research.